Description: (Applicant's Description) Gastric cancer is the eleventh leading cause of cancer-related deaths in the United States and remains one of the most serious worldwide health burdens. Upper endoscopy is effective in the diagnosis of gastric cancer and surgery for localized disease is usually curative. The majority of gastric cancer patients, however, are diagnosed at a late stage of the disease and die soon after diagnosis. Studies have not identified subgroups of patients in whom screening to detect early gastric cancer may be effective. Further gastric cancer studies are needed to determine its environmental and genetic risk factors particularly using population-based patients and their families so that cancer prevention and control strategies can be developed. We propose to integrate techniques in genetic epidemiology and molecular biology to develop a means of identifying and characterizing inherited gastric cancer predisposing syndromes. The model will consider genetic factors that may be associated with tumor aggressiveness, environmental exposures and interactions among these factors. We will assemble a population-based series of approximately 350 gastric cancer cases and controls to assess the etiologic component associated with familial and potentially hereditary predisposition and to compare clinical, pathologic and prognostic features in sporadic, familial, and potentially hereditary gastric cancer. Methods already developed by the Epidemiology Division of UCI will be used to collect family history, epidemiologic risk factors, biologic samples (serum, lymphocytes, and paraffin-embedded tumor and normal tissue). We will test all gastric cancer cases for the replication error phenotype at microsatellites at seven loci. We will also test patient serum for IgG to Helicobacter pylori. Gene testing will be done on potential hereditary cases, focusing on the p53 and mismatch repair gene loci. This case-control study of possible genetic mutations will allow identification of populations at high risk for this cancer where opportunities for prevention and early detection of gastric cancer can be realized.